The IntAct database: efficient access to fine-grained molecular interaction data

Toro, Noemí del; Shrivastava, Anjali; Ragueneau, Eliot; Meldal, Birgit; Combe, Colin; Barrera, Elisabet; Perfetto, Livia; How, Karyn; Ratan, Prashansa; Shirodkar, Gautam; Lu, Odilia; Mészáros, Bálint; Watkins, Xavier; Pundir, Sangya; Licata, Luana; Iannuccelli, Marta; Pellegrini, Matteo; Martin, Maria Jesus; Panni, Simona; Duesbury, Margaret; Vallet, Sylvain D.; Rappsilber, Juri; Ricard‐Blum, Sylvie; Cesareni, Gianni; Salwiński, Łukasz; Orchard, Sandra; Porras, Pablo; Panneerselvam, Kalpana; Hermjakob, Henning

doi:10.1093/nar/gkab1006

Cited by 182 publications

(114 citation statements)

References 30 publications

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“…Elsewhere, an Update paper from CAZy ( 51 ), the database of carbohydrate-active enzymes, reports significant increases in numbers of enzyme families alongside interface improvements including Krona charts ( 52 ) for taxonomic distributions of families. Finally, sister EBI resources for macromolecular interactions IntAct ( 53 ) and Complex Portal ( 54 ) each contribute an Update. IntAct has more than doubled in size since its previous publication and captures diverse information on binary molecular interactions, including a SARS-CoV-2 interactome, in particularly clean and appealing visualisations.…”

Section: New and Updated Databasesmentioning

confidence: 99%

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Rigden

Fernández

2021

Nucleic Acids Research

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The 2022 Nucleic Acids Research Database Issue contains 185 papers, including 87 papers reporting on new databases and 85 updates from resources previously published in the Issue. Thirteen additional manuscripts provide updates on databases most recently published elsewhere. Seven new databases focus specifically on COVID-19 and SARS-CoV-2, including SCoV2-MD, the first of the Issue's Breakthrough Articles. Major nucleic acid databases reporting updates include MODOMICS, JASPAR and miRTarBase. The AlphaFold Protein Structure Database, described in the second Breakthrough Article, is the stand-out in the protein section, where the Human Proteoform Atlas and GproteinDb are other notable new arrivals. Updates from DisProt, FuzDB and ELM comprehensively cover disordered proteins. Under the metabolism and signalling section Reactome, ConsensusPathDB, HMDB and CAZy are major returning resources. In microbial and viral genomes taxonomy and systematics are well covered by LPSN, TYGS and GTDB. Genomics resources include Ensembl, Ensembl Genomes and UCSC Genome Browser. Major returning pharmacology resource names include the IUPHAR/BPS guide and the Therapeutic Target Database. New plant databases include PlantGSAD for gene lists and qPTMplants for post-translational modifications. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Our latest update to the NAR online Molecular Biology Database Collection brings the total number of entries to 1645. Following last year's major cleanup, we have updated 317 entries, listing 89 new resources and trimming 80 discontinued URLs. The current release is available at http://www.oxfordjournals.org/nar/database/c/.

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Section: New and Updated Databasesmentioning

confidence: 99%

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Rigden

Fernández

2021

Nucleic Acids Research

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“…By design, the original PRECOG and the corresponding model trained on the GEMTA assay using hand-crafted features (see below) only considered class A GPCRs. For testing β-arrestin models, we considered 57 Class A GPCR - β-arrestin 1/2 interactions obtained from STRING (combined score > 600) ( 26 ), HIPPIE ( 27 ), and IMEx ( 28 ) databases. We finally selected the 17 best performing models for each G protein or β-arrestin based on the highest Recall during testing.…”

Section: Methodsmentioning

confidence: 99%

PRECOGx: exploring GPCR signaling mechanisms with deep protein representations

Matic

Singh

Carli

et al. 2022

Nucleic Acids Research

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In this study we show that protein language models can encode structural and functional information of GPCR sequences that can be used to predict their signaling and functional repertoire. We used the ESM1b protein embeddings as features and the binding information known from publicly available studies to develop PRECOGx, a machine learning predictor to explore GPCR interactions with G protein and β-arrestin, which we made available through a new webserver (https://precogx.bioinfolab.sns.it/). PRECOGx outperformed its predecessor (e.g. PRECOG) in predicting GPCR-transducer couplings, being also able to consider all GPCR classes. The webserver also provides new functionalities, such as the projection of input sequences on a low-dimensional space describing essential features of the human GPCRome, which is used as a reference to track GPCR variants. Additionally, it allows inspection of the sequence and structural determinants responsible for coupling via the analysis of the most important attention maps used by the models as well as through predicted intramolecular contacts. We demonstrate applications of PRECOGx by predicting the impact of disease variants (ClinVar) and alternative splice forms from healthy tissues (GTEX) of human GPCRs, revealing the power to dissect system biasing mechanisms in both health and disease.

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“…These public resources can be divided in: (i ) primary databases that collect only manually curated molecular interactions extracted from peer-reviewed journals and related to different viruses and their relative hosts, such as MINT ( Calderone et al, 2020 ), IntAct ( Del Toro et al, 2021 ), and BioGRID ( Oughtred et al, 2021 ); ( ii ) metadatabases integrating data from primary resources, such as VirusMentha ( Calderone et al, 2015 ) and APID ( Alonso-López et al, 2019 ); ( iii ) databases combining experimental interaction data with predicted PPIs, such as virusSTRING ( Szklarczyk et al, 2021 ), human-virus PPI database (HVIDB) ( Yang et al, 2021 ) and the pathogen-host interaction search tool PHISTO ( Durmuş Tekir et al, 2013 ); ( iv ) databases, such as VirHostnet3.0 database ( Guirimand et al, 2015 ), which are both primary resources collecting manually annotated PPIs and metadatabases integrating data from other molecular interaction databases; and ( v ) databases collecting information only related to a specific virus-host interactome, such as DenHunt ( Karyala et al, 2016 ) and DenvInt ( Dey and Mukhopadhyay, 2017 ) for the Dengue virus, the HIV-1 Human Interaction Database ( Ako-Adjei et al, 2015 ) and the Hepatitis C Virus Protein Interaction Database (HCVpro) ( Kwofie et al, 2011 ).…”

Section: Public Resources Collecting Virus-host Protein-protein Inter...mentioning

confidence: 99%

“…Over the years, these interaction maps described in the scientific literature have been systematically captured into several publicly available molecular interaction databases (e.g., Guirimand et al, 2015 ; Calderone et al, 2020 ; Del Toro et al, 2021 ; Oughtred et al, 2021 ). The interaction data is organized in structured formats ( Orchard et al, 2007 ; Porras et al, 2020 ), that can be easily processed and exploited to perform downstream computational and network analyses ( Porras et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Intricacy of the Viral-Human Protein Interaction Networks: Resources, Data, and Analyses

et al. 2022

Self Cite

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Viral infections are one of the major causes of human diseases that cause yearly millions of deaths and seriously threaten global health, as we have experienced with the COVID-19 pandemic. Numerous approaches have been adopted to understand viral diseases and develop pharmacological treatments. Among them, the study of virus-host protein-protein interactions is a powerful strategy to comprehend the molecular mechanisms employed by the virus to infect the host cells and to interact with their components. Experimental protein-protein interactions described in the scientific literature have been systematically captured into several molecular interaction databases. These data are organized in structured formats and can be easily downloaded by users to perform further bioinformatic and network studies. Network analysis of available virus-host interactomes allow us to understand how the host interactome is perturbed upon viral infection and what are the key host proteins targeted by the virus and the main cellular pathways that are subverted. In this review, we give an overview of publicly available viral-human protein-protein interactions resources and the community standards, curation rules and adopted ontologies. A description of the main virus-human interactome available is provided, together with the main network analyses that have been performed. We finally discuss the main limitations and future challenges to assess the quality and reliability of protein-protein interaction datasets and resources.

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The IntAct database: efficient access to fine-grained molecular interaction data

Cited by 182 publications

References 30 publications

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

PRECOGx: exploring GPCR signaling mechanisms with deep protein representations

The Intricacy of the Viral-Human Protein Interaction Networks: Resources, Data, and Analyses

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